Using default constraints of the spindle assembly checkpoint to estimate the associated chemical rates.
Bottom Line:
Our purpose is to use these opposed constraints to estimate the associated chemical rates.We compute the probability for no APC/C activation before time t, the distribution of Cdc20 at equilibrium and the mean time to complete APC/C activation after all chromosomes are attached.By studying Cdc20 inhibition and the activation time, we obtain a range for the main chemical reaction rates regulating the spindle assembly checkpoint and transition to anaphase.
Affiliation: Institute for Biology (IBENS), Group of Computational Biology and Applied Mathematics, Ecole Normale Supérieure, 46 rue d'Ulm 75005 Paris, France. holcman@ens.fr.
ABSTRACT
Unlabelled: : Background: Default activation of the spindle assembly checkpoint provides severe constraints on the underlying biochemical activation rates: on one hand, the cell cannot divide before all chromosomes are aligned, but on the other hand, when they are ready, the separation is quite fast, lasting a few minutes. Our purpose is to use these opposed constraints to estimate the associated chemical rates. Results: To analyze the above constraints, we develop a markovian model to describe the dynamics of Cdc20 molecules. We compute the probability for no APC/C activation before time t, the distribution of Cdc20 at equilibrium and the mean time to complete APC/C activation after all chromosomes are attached. Conclusions: By studying Cdc20 inhibition and the activation time, we obtain a range for the main chemical reaction rates regulating the spindle assembly checkpoint and transition to anaphase. No MeSH data available. Related in: MedlinePlus |
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Mentions: In practice, we solve this linear system of equations numerically and in figure 5, we plot the mean τ as a function of the parameters k-1 and λ. We find that τ is a decreasing function of λ (the faster Cdc20 is produced, the faster the threshold of bindings is reached) and an increasing function of the rate k-1 (inhibition decreases the number of Cdc20 at equilibrium and thus the time to reach the threshold, after the source of inhibition is terminated). These variations go in the opposite direction compared to the probability of no activation during the SAC. Thus we expect that using the probability P and this mean time τ will lead to limit the range of the parameters λ and k-1 as we will describe now. |
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Affiliation: Institute for Biology (IBENS), Group of Computational Biology and Applied Mathematics, Ecole Normale Supérieure, 46 rue d'Ulm 75005 Paris, France. holcman@ens.fr.
Unlabelled: :
Background: Default activation of the spindle assembly checkpoint provides severe constraints on the underlying biochemical activation rates: on one hand, the cell cannot divide before all chromosomes are aligned, but on the other hand, when they are ready, the separation is quite fast, lasting a few minutes. Our purpose is to use these opposed constraints to estimate the associated chemical rates.
Results: To analyze the above constraints, we develop a markovian model to describe the dynamics of Cdc20 molecules. We compute the probability for no APC/C activation before time t, the distribution of Cdc20 at equilibrium and the mean time to complete APC/C activation after all chromosomes are attached.
Conclusions: By studying Cdc20 inhibition and the activation time, we obtain a range for the main chemical reaction rates regulating the spindle assembly checkpoint and transition to anaphase.
No MeSH data available.